Innate immunity and metabolic shifts in cells using the Alternative Lengthening of Telomeres mechanism
(2025)
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- Authors
- Supervisors
- Decottignies, Anabelle
- Abstract
- Telomere maintenance is essential for cancer cell survival and relies on either telomerase or the ALT mechanism which is frequent in paediatric tumours and absent from normal cells. This work compares ALT+ and TEL+ cells to identify ALT- specific vulnerabilities. Multi-omic analyses revealed signatures involving innate immunity, ER stress and lipid metabolism which may reflect adaptations to chronic replication stress in ALT+ cells. ALT+ cells displayed active cGAS-STING signalling, higher interferon-stimulated genes and a reliance on autophagy for pathway regulation. They showed increased resistance to ER stress and ferroptosis, linked to altered ATL1, NUP210 and ATGL levels and changes in PUFA metabolism. PUFA-derived lipids may also influence the microenvironment of ALT tumours. Overall, these findings reveal immune and metabolic features of ALT+ cells that could inform future studies on their biology and vulnerabilities.
- Affiliations
Citations
Geelen, D. (2025). Innate immunity and metabolic shifts in cells using the Alternative Lengthening of Telomeres mechanism.